Glaucoma and Ocular Surface Disease: Differentiating Between Disease and Treatment Side Effects

1
Glaucoma and Ocular Surface Disease
Differentiating Between Disease and Treatment
Side Effects

• Robert D. Fechtner, MD
• Professor of Ophthalmology
• Director, Glaucoma Division
• Institute of Ophthalmology and Visual Science
• New Jersey Medical School UMDNJ
• Newark, New Jersey
• Clark L. Springs, MD
• Assistant Professor
• Director of Cornea and Refractory Surgery
• Glick Eye Institute
• Indiana University School of Medicine
• Indianapolis, Indiana

2
Overall Program Goal

• The goal of the program is to examine the
  incidence of and issues involved in accurately
  identifying and managing ocular surface disease
  in patients who have glaucoma.

3
Prevalence of Dry Eye and Ocular Surface Disease

• Study results showing prevalence of dry eye
  (overall, in women, in men, and in older
  individuals)
• Schaumberg DA, et al. Am J Ophthalmol.
  2003136318-326.
• Schaumberg DA, et al. Arch Ophthalmol.
  2009127763-768.
• Schein OD, et al. Am J Ophthalmol.
  1997124723-728.

4
Prevalence of Dry Eye Among Women Study
Population

• 39,876 health professionals
• Ages 45-84 years
• Enrolled in the Womens Health Study, a
  randomized trial designed to assess the benefits
  of and risks for aspirin and vitamin E in the
  primary prevention of cardiovascular disease and
  cancer in healthy women
• Participants received mailed questionnaires every
  year
• At year 4, included 3 questions about dry eye

Schaumberg DA, et al. Am J Ophthalmol.
2003136318-326.
5
Prevalence of Dry Eye Among Women Methods

• Have you ever been diagnosed by a clinician as
  having dry eye syndrome?
• How often do your eyes feel dry (not wet enough)?
  
• How often do your eyes feel irritated?
• Possible answers
• constantly
• often
• sometimes
• never

Schaumberg DA, et al. Am J Ophthalmol.
2003136318-326.
6
Prevalence of Dry Eye Among Women Results

• The prevalence of dry eye syndrome increased with
  age, from 5.7 among women lt 50 years old to 9.8
  among women aged gt 75 years old. The age-adjusted
  prevalence of dry eye syndrome was 7.8, or 3.23
  million women aged gt 50 in the United States.
• Compared with whites, Hispanic (OR 1.81, CI
  1.18-2.80) and Asian (OR 1.77, CI 1.17-2.69)
  women were more likely to report severe symptoms,
  but not be clinically diagnosed with dry eye
  syndrome.
• Women from the South had the highest prevalence
  of dry eye syndrome, although the magnitude of
  geographic differences was modest.

Schaumberg DA, et al. Am J Ophthalmol.
2003136318-326.
7
Prevalence of Dry Eye Among Women

• 9.8 among women aged gt 75 years old

Schaumberg DA, et al. Am J Ophthalmol.
2003136318-326.
8
Prevalence of Dry Eye Among Men Study Population

• Physicians Health Study (PHS)
• Randomized period of PHS I and PHS II ended in
  1999
• 25,444 men, including 18,596 original
  participants in PHS I and 6848 men who did not
  participate in PHS I but were randomly assigned
  to PHS II

Schaumberg DA, et al. Arch Ophthalmol.
2009127763-768.
9
Prevalence of Dry Eye Among Men Methods

• Have you ever been diagnosed by a clinician as
  having dry eye syndrome?
• How often do your eyes feel dry (not wet enough)?
• How often do your eyes feel irritated?
• Possible answers
• constantly
• often
• sometimes
• never

Schaumberg DA, et al. Arch Ophthalmol.
2009127763-768.
10
Prevalence of Dry Eye Among Men Results

• The prevalence of dry eye disease increased with
  age, from 3.90 among men aged 50-54 years to
  7.67 among men 80 years and older (P for trend
  .001).
• High blood pressure and benign prostatic
  hyperplasia were associated with a higher risk
  for dry eye disease.
• Use of antidepressants, antihypertensives, and
  medications to treat benign prostatic hyperplasia
  were also associated with increased risk for dry
  eye disease.

Schaumberg DA, et al. Arch Ophthalmol.
2009127763-768.
11
Prevalence of Dry Eye Among Men

• 7.67 among men 80 years and older

Schaumberg DA, et al. Arch Ophthalmol.
2009127763-768.
12
Prevalence of Dry Eye Among the Elderly Study
Population

• 2520 residents of Salisbury, Maryland
• 65 years or older as of 1993
• Standardized questionnaire (6 questions)
• Examination
• Schirmers test
• Rose Bengal stain
• Assessment of meibomian glands

Schein OD, et al. Am J Ophthalmol.
1997124723-728.
13
Prevalence of Dry Eye Among the Elderly Results
Age Group (yr) Percent Who Have 1 or More Symptoms Often or All the Time
65-69 14.2 (774)
70-74 14.9 (824)
75-79 13.7 (540)
80 16.3 (344)
Gender
Male 13.3 (1052)
Female 15.6 (1430)
Schein OD, et al. Am J Ophthalmol.
1997124723-728.
14
Prevalence of Dry Eye Among the Elderly Results

• 14.6 reported 1 or more dry eye symptom often
  or all the time

Schein OD, et al. Am J Ophthalmol.
1997124723-728.
15
Interactive Poll Question

• Approximately what percentage of your patients
  treated for glaucoma also have ocular surface
  disease symptoms?
• ? Fewer than 1
• ? Approximately 10
• ? Approximately 25
• ? Approximately 50
• ? More than half

16
Prevalence of Ocular Surface Disease in Patients
With Glaucoma

• Studies have sought to determine how common
  ocular surface disease (OSD) is in patients with
  glaucoma
• Leung EW, et al. J Glaucoma. 2008 17350-355.
• Fechtner RD, et al. Cornea. 201029618-621.

17
Prevalence of OSD in Patients With Glaucoma
Study Design

• 101 patients with glaucoma or ocular hypertension
• Exclusions receiving cyclosporine, steroids,
  topical ocular nonsteroidal anti-inflammatory
  drugs, or punctal plugs within previous 3 months
• Testing
• Ocular Surface Disease Index (OSDI)
• Schirmers test
• Staining (fluorescein and lissamine green)
• Tear break-up time (TBUT)

Leung EW, et al. J Glaucoma. 200817350-355.
18
Number () of Patients With Each Result
Test Results Lissamine Green OSDI Schirmers Test TBUT
Normal 79 41 39 22
Mild to Moderate 22 33 27 13
Severe 0 27 35 66
Leung EW, et al. J Glaucoma. 200817350-355.
19
Symptoms vs Signs of OSD
Patients With Symptoms ()
Clinical Tests
Leung EW, et al. J Glaucoma. 200817350-355.
20
Prevalence of OSD in Patients With Glaucoma
Results
OSDI Scores in Glaucoma Patients
Ranking Normal Mild to Moderate Severe
Patients 41 33 27
Percentage 41 33 27
59
Leung EW, et al. J Glaucoma. 200817350-355.
21
Prevalence of OSD in Patients With Glaucoma
Treated With Topical Medications Study Methods

• Conducted from May 2006 to March 2007
• 10 sites - geographically distributed
• 630 glaucoma patients
• gt 18 years of age
• Primary open-angle, exfoliation, or pigment
  dispersion glaucoma, or ocular hypertension in
  both eyes
• Treated with 1 or more topical intraocular
  pressure-lowering medication(s)
• Patients completed OSDI survey while in the office

Fechtner RD, et al. Cornea. 201029618-621.
22
OSDI Severity Grading
Normal (0-12)
Mild (13-22)
Moderate (23-32)
Severe (33-100)
0
10
20
30
40
50
60
70
80
90
100
Total OSDI Score (Sum of Score for All
Questions Answered) X (25) (Total of Questions
Answered)
Miller KL, et al. 13th Annual Conference of
the International Society for Quality of Life
Research. 2006. Abstract 1540.
23
Prevalence of OSD in Patients With Glaucoma
Treated With Topical Medications Study Results
OSDI Scores in Glaucoma Patients
Ranking Normal Mild Moderate Severe
Patients 325 134 84 87
Percentage 51.6 21.3 13.3 13.8
48.4
Fechtner RD, et al. Cornea. 201029618-621.
24
Ocular Surface Disease and Topical Medications
for Glaucoma

• Studies suggest there may be a relationship
  between the presence of OSD in patients with
  glaucoma and topical medications for glaucoma
• Leung EW, et al. J Glaucoma. 200817350-355.
• Rossi GC, et al. Eur J Ophthalmol.
  200919572-579.

25
OSDI and Number of BAK-Containing Eyedrops
Patients (Percentage)
Number of BAK-Containing Eyedrops
BAK benzalkonium chloride Leung EW, et al. J
Glaucoma. 200817350-355.
26
Quality of Life Study Methods

• 61 treated subjects (G1 1 drop/day, G2 2
  drops/day, G3 3 drops/day)
• 20 untreated controls (G0 no drops)
• Questionnaires
• National Eye Institute Visual Function
  Questionnaire (NEI-VFQ)
• Glaucoma Symptom Scale (GSS)
• OSDI
• Dry eye syndrome was defined as presence of
  punctate keratitis and decreased TBUT

Rossi GC, et al. Eur J Ophthalmol.
200919572-579.
27
Quality of Life Impact of Multiple Medications
Number of Medications Percent With Dry Eye Syndrome
0 medications 5
1 medication 11
2 medications 39
3 medications 40
Rossi GC, et al. Eur J Ophthalmol.
200919572-579.
28
Discussion of Answers to Poll Question
29
Case 1 A 55-Year-Old Man

• 55-year-old psychiatrist
• Medical History
• Panic attacks (started 1 month ago)
• Ocular History
• Primary open-angle glaucoma (diagnosed 15 years
  ago)
• Posterior chamber intraocular lens OU
• Trabeculectomy OU
• Presumed ocular histoplasmosis syndrome OU, with
  central macular scars OU

OU each eye
30
Case 1 Medications

• Ocular Medications
• Bimatoprost OU every evening
• Other Medications
• Escitalopram (for panic attacks)

31
Chief Complaint

• I am uncomfortable driving and I have difficulty
  reading at work.

32
Case 1 Examination

• BCVa 20/400 OD
• OS vision decreased from 20/50 to 20/100
• IOP in mid-teens
• Moderate rosacea with meibomian gland dysfunction
  
• Severe central PEE
• Normal Schirmers test
• Has to wear SCL to make bioptics work
• Torn SCL

BCVa best corrected visual acuity OD right
eye OS left eye IOP intraocular pressure
PEE punctate epithelial erosions SCL soft
contact lens
33
Interactive Poll Question

• How would you proceed in this patient?
• ? Change to preservative-free artificial tears
• ? Decrease BAK load
• ? Anti-inflammatory therapy
• ? Punctal plugs
• ? All of the above

34
Case 1 Treatment Plan

• Reduce BAK Load
• Travoprost BAK-free substituted for
  bimatoprosta-c
• Anti-inflammatory therapy
• Loteprednol etabonated
• 4 times a day for 1 week, thrice daily for 1
  week, twice daily for 1 week, once daily for 1
  week
• Cyclosporine OU twice dailye
• Doxycycline 20 mg orally twice dailyf

a. Baudouin C, et al. Br J Ophthalmol.
19988239-42. b. Pisella PJ, et al. Br J
Ophthalmol. 200286418-423. c. Jaenen N, et al.
Eur J Ophthalmol. 200717341-351. d. Pavesio CE,
Decory HH. Br J Ophthalmol. 200892455-459. e.
Perry HD, et al. Cornea. 200625171-175. f.
Stone DU, Chodosh J. Cornea. 200423106-109.
35
Case 1 Follow-up

• 4-week follow-up BCVa improved to 20/60 left eye
• 1-year follow-up BCVa improved to baseline

36
Discussion of Answers to Poll Question
37
Discussion Approach to Patient
38
Case 2 An 86-Year-Old Man

• 86-year-old white man
• Medical history
• Hypertension
• Cerebrovascular disease
• Heart disease
• Ocular history
• Primary open-angle glaucoma since 1998
• Cataract extraction with intraocular lens OU 2000
• Branch retinal vein occlusion (BRVO) OD with poor
  vision 2002
• Steroid responder
• Family history sisters with glaucoma

39
Case 2 Medications

• Medications verapamil, lisinopril, propafenone,
• simvastatin, dronedarone , aspirin
• Ocular medications bimatoprost at bedtime OU,
  brimonidine/timolol twice daily OU, cyclosporine
  ophthalmic twice daily OU, methazolamide 50 mg
  thrice daily, artificial tears as needed
• Allergies All glaucoma drops

40
Chief Complaint
When I use my glaucoma medications and my IOP is
controlled, my vision is poor. When I stop my
drops, I see much better but my IOP is in the
30s.
41
Case 2. Ocular Examination

• Visual acuity distance OD 20/150, (0.50-4.00 X
  005), OS 20/50 (1.0-3.50 X 90) ph 20/30-2
• External examination
• Lids erythema and meibomian gland dysfunction
• Conjunctiva 2 injection OU
• Cornea punctate staining
• Anterior chamber quiet
• Lens IOL
• Extraocular movement unremarkable
• Pupils afferent defect OD

42
Case 2. Slit Lamp Examination

• Lids meibomian gland dysfunction
• Conjunctiva 2 injection
• Cornea punctate staining OU
• Anterior chamber OU, deep, quiet
• Iris OU normal
• IOP OD, 14 mm Hg, OS 19 mm Hg
• Pachymetry 560 OD, 552 OS
• Gonioscopy OU, open, ciliary body showing
  (d-40-q)

43
Interactive Poll Question

• What are possible contributors to the external
  signs and symptoms?
• ? Drug allergy
• ? Drug toxicity
• ? Dry eye
• ? Meibomian gland disease
• ? Preservative toxicity

44
Case 2. Dilated Examination and Diagnostic
Testing

• Lens OU, IOL
• Disc OD, CDR 0.9OS, CDR 0.5- (VH)
• Retina OD old BRVO

45
Optic Nerve
ltltHold for photogtgt
46
Visual Field HVF 24-2
47
(No Transcript)
48
Discussion of Answers to Poll Question
49
Case 2 Treatment Plan

• Reduce BAK loada-c
• Discontinue bimatoprost and brimonidine/timolol
• Begin travoprost with sofZia preservative and
  preservative-free timolol
• Continue methazolamide
• Treat meibomian gland disease and ocular surface
• Lid hygiene
• Add azithromycin ophthalmicd
• Continue cyclosporine ophthalmic

a. Baudouin C, et al. Br J Ophthalmol.
19988239-42. b. Pisella PJ, et al. Br J
Ophthalmol. 200286418-423. c. Jaenen N, et al.
Eur J Ophthalmol. 200717341-9.15. d. Luchs J.
Adv Ther. 200825858-870.
50
Case 2 Follow-up

• Two weeks later, by telephone call I feel a
  little better
• One week after that
• Seen by comprehensive ophthalmologist
• Felt fine, felt vision was better
• IOP 30s OU
• Treated with brimonidine and brimonidine/timolol
  in the office
• Placed on brimonidine 0.15 with Polyquad

51
Medications

• Travoprost OU at bedtime
• Preservative-free timolol OU twice daily
• Brimonidine 0.15 OU thrice daily
• Azithromycin ophthalmic OU twice daily
• Cyclosporine ophthalmic OU twice daily
• Methazolamide 50 mg orally thrice daily

52
Case 2 Follow-up Examination

• Visual acuity 20/150 OD, 20/50 OS
• Lids and eyes red
• Conjunctiva 2 injection with follicles
• Cornea mild punctate staining

53
Case 2 Suspected Brimonidine Allergy

• Discontinue brimonidine, cyclosporine ophthalmic,
  
• azithromycin ophthalmic
• Continue travoprost, preservative-free timolol,
• methazolamide
• Add pilocarpine 1 thrice daily OU, olopatadine
  once daily OU, doxycyline 20 mg orally once daily

Blondeau P, Rousseau JA. Can J Ophthalmol.
20023721-26.
54
Discussion Approach to Patient
55
Question-and-Answer Session With the Audience
56
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